Evidence map›Paper›PMID 27071670›Full record

ArticleArthritis research & therapy2016

Inflammatory properties of inhibitor of DNA binding 1 secreted by synovial fibroblasts in rheumatoid arthritis.

Gautam Edhayan, Ray A Ohara, W Alex Stinson, M Asif Amin, Takeo Isozaki, Christine M Ha, G Kenneth Haines, Rachel Morgan, Phillip L Campbell, Ali S Arbab and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.0field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 32 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Gautam EdhayanDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, 109 Zina Pitcher Drive, 4023 BSRB, Ann Arbor, MI, 48109-2200, USA.
Ray A OharaDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, 109 Zina Pitcher Drive, 4023 BSRB, Ann Arbor, MI, 48109-2200, USA.
W Alex StinsonDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, 109 Zina Pitcher Drive, 4023 BSRB, Ann Arbor, MI, 48109-2200, USA.
M Asif AminDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, 109 Zina Pitcher Drive, 4023 BSRB, Ann Arbor, MI, 48109-2200, USA.
Takeo IsozakiDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, 109 Zina Pitcher Drive, 4023 BSRB, Ann Arbor, MI, 48109-2200, USA.
Christine M HaDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, 109 Zina Pitcher Drive, 4023 BSRB, Ann Arbor, MI, 48109-2200, USA.
G Kenneth HainesMount Sinai Health System, New York, NY, 10019, USA.
Rachel MorganDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, 109 Zina Pitcher Drive, 4023 BSRB, Ann Arbor, MI, 48109-2200, USA.
Phillip L CampbellDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, 109 Zina Pitcher Drive, 4023 BSRB, Ann Arbor, MI, 48109-2200, USA.
Ali S ArbabHenry Ford Hospital, Detroit, MI, 48202, USA.
Sean C FridayDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, 109 Zina Pitcher Drive, 4023 BSRB, Ann Arbor, MI, 48109-2200, USA.
David A FoxDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, 109 Zina Pitcher Drive, 4023 BSRB, Ann Arbor, MI, 48109-2200, USA.
Jeffrey H RuthDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, 109 Zina Pitcher Drive, 4023 BSRB, Ann Arbor, MI, 48109-2200, USA. jhruth@umich.edu.
University of Michigan–Ann Arbor · USHenry Ford Hospital · USMount Sinai Health System · US

Funding

University of Michigan Clinical Autoimmunity Center of ExcellenceUM1AI144298 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FOX, DAVID ALAN, KHANNA, DINESH · 2019 to 2023
$546k
University of Michigan Autoimmunity Center of Excellence, Clinical Research ProgrUM1AI110557 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FOX, DAVID ALAN · 2014 to 2018
$543k
NIAID NIH HHS UM1 AI110557NIAID NIH HHS UM1 AI144298
6 · The paper itself

Abstract

backgroundInhibitor of DNA binding 1 (Id1) is a nuclear protein containing a basic helix-loop-helix (bHLH) domain that regulates cell growth by selective binding and prevention of gene transcription. Sources of Id1 production in rheumatoid arthritis synovial tissue (RA ST) and its range of functional effects in RA remain to be clarified.

methodsWe analyzed Id1 produced from synovial fibroblasts and endothelial cells (ECs) with histology and real-time polymerase chain reaction (RT-PCR). Fibroblast supernatants subjected to differential centrifugation to isolate and purify exosomes were measured for Id1 by enzyme-linked immunosorbent assay (ELISA). Western blotting of Id1-stimulated ECs was performed to determine the kinetics of intracellular protein phosphorylation. EC intracellular signaling pathways induced by Id1 were subsequently targeted with silencing RNA (siRNA) for angiogenesis inhibition.

resultsBy PCR and histologic analysis, we found that the primary source of Id1 in STs is from activated fibroblasts that correlate with inflammatory scores in human RA ST and in joints from K/BxN serum-induced mice. Normal (NL) and RA synovial fibroblasts increase Id1 production with stimulation by transforming growth factor beta (TGF-β). Most of the Id1 released by RA synovial fibroblasts is contained within exosomes. Endothelial progenitor cells (EPCs) and human dermal microvascular ECs (HMVECs) activate the Jnk signaling pathway in response to Id1, and Jnk siRNA reverses Id1-induced HMVEC vessel formation in Matrigel plugs in vivo.

conclusionsId1 is a pleotropic molecule affecting angiogenesis, vasculogenesis, and fibrosis. Our data shows that Id1 is not only an important nuclear protein, but also can be released from fibroblasts via exosomes. The ability of extracellular Id1 to activate signaling pathways expands the role of Id1 in the orchestration of tissue inflammation.

Indexed as

AnimalsArthritis, ExperimentalArthritis, RheumatoidBlotting, WesternCells, CulturedEnzyme-Linked Immunosorbent AssayFibroblastsFluorescent Antibody TechniqueHumansImmunohistochemistryInflammationInhibitor of Differentiation Protein 1MiceMice, Inbred C57BLMice, SCIDReal-Time Polymerase Chain ReactionInhibitor of Differentiation Protein 1AngiogenesisFibroblastsInflammationInhibitor of DNA binding-1 protein (Id1)Rheumatoid arthritis

Identifiers

PMID27071670
PMCPMC4830090
OpenAlexW2338845178

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.